Assessing the impact of the COVID-19 restrictions on HIV testing services in Malawi: an interrupted time series analysis.

Background: Restrictions on public gatherings and movement to mitigate the spread of COVID-19 may have disrupted access and availability of HIV services in Malawi. We quantified the impact of these restrictions on HIV testing services in Malawi.Methods: We conducted an interrupted time series analysis of routine aggregated programme data from 808 public and private, adult and paediatric health facilities across rural and urban communities in Malawi between January 2018 and March 2020 (pre-restrictions) and April to December 2020 (post restrictions), with April 2020 as the month restrictions took effect. Positivity rates were expressed as the proportion of new diagnoses per 100 persons tested. Data were summarised using counts and median monthly tests stratified by sex, age, type of health facility and service delivery points at health facilities. The immediate effect of restriction and post-lockdown outcomes trends were quantified using negative binomial segmented regression models adjusted for seasonality and autocorrelation.Results: The median monthly number of HIV tests and diagnosed people living with HIV (PLHIV) declined from 261 979 (interquartile range [IQR] 235 654-283 293) and 7 929 (IQR 6 590-9 316) before the restrictions, to 167 307 (IQR 161 122-185 094) and 4 658 (IQR 4 535-5 393) respectively, post restriction. Immediately after restriction, HIV tests declined by 31.9% (incidence rate ratio [IRR] 0.681; 95% CI 0.619-0.750), the number of PLHIV diagnosed declined by 22.8% (IRR 0.772; 95% CI 0.695-0.857), while positivity increased by 13.4% (IRR 1.134; 95% CI 1.031-1.247). As restrictions eased, total HIV testing outputs and the number of new diagnoses increased by an average of 2.3% each month (slope change: 1.023; 95% CI 1.010-1.037) and 2.5% (slope change:1.025; 95% CI 1.012-1.038) respectively. Positivity remained similar (slope change: 1.001; 95% CI 0.987-1.015). Unlike general trends noted, while HIV testing services among children aged <12 months declined 38.8% (IRR 0.351; 95% CI 0.351-1.006) with restrictions, recovery has been minimal (slope change: 1.008; 95% CI 0.946-1.073).Conclusion: COVID-19 restrictions were associated with significant but short-term declines in HIV testing services in Malawi, with differential recovery in these services among population subgroups, especially infants. While efforts to restore HIV testing services are commendable, more nuanced strategies that promote equitable recovery of HIV testing services can ensure no subpopulations are left behind.

HIV Testing Approaches to Optimize Prevention and Treatment for Key and Priority Populations in Malawi.

Background: Despite progress in improving antiretroviral therapy (ART) for people with HIV in Malawi, the burden of HIV infections and HIV treatment outcomes among key populations is suboptimal. Client-centered differentiated service delivery approaches may facilitate addressing HIV prevention and treatment needs of key populations in Malawi. Methods: De-identified program data routinely collected as part of the LINKAGES project-Malawi were assembled from October 2017 to September 2019. HIV case finding was compared across different testing modalities for each population. Poisson regression was used to estimate the association between testing modalities and ART initiation. Results: Of the 18 397 people included in analyses, 10 627 (58%) were female sex workers (FSWs), 2219 (12%) were men who have sex with men (MSM), and 4970 (27%) were clients of FSWs. HIV case finding varied by modality and population, with index testing and enhanced peer outreach demonstrating high yield despite reaching relatively few individuals. FSWs who tested positive through risk network referral testing were more likely to initiate ART within 30 days compared with those who tested positive through clinic-based testing (adjusted risk ratio [aRR], 1.50; 95% CI, 1.23-1.82). For MSM, index testing (aRR, 1.45; 95% CI, 1.06-2.00) and testing through a drop-in center (aRR, 1.82; 95% CI, 1.19-2.78) were associated with 30-day ART initiation. Conclusions: These data suggest that differentiated HIV testing and outreach approaches tailored to the needs of different key populations may facilitate improved ART initiation in Malawi. Achieving 0 new infections by 2030 suggests the need to adapt treatment strategies given individual and structural barriers to treatment for key populations with HIV in high-prevalence settings.

Readiness for Use of HIV Preexposure Prophylaxis Among Men Who Have Sex With Men in Malawi: Qualitative Focus Group and Interview Study.

BACKGROUND: Men who have sex with men (MSM) are a key group for HIV interventions in Malawi considering their high HIV prevalence (17.5% compared to 8.4% among men in the general population). The use of oral preexposure prophylaxis (PrEP) presents a new opportunity for MSM to be protected. We present the findings from a qualitative assessment designed to assess awareness of and willingness and barriers to using PrEP among MSM in Malawi. OBJECTIVE: The 3 main objectives of this assessment were to determine: (1) awareness of PrEP, (2) factors that influence willingness to use PrEP, and (3) potential barriers to PrEP use and adherence among MSM in order to guide the design and implementation of a PrEP program in Malawi. METHODS: Ahead of the introduction of PrEP in Malawi, a qualitative study using in-depth interviews (IDIs) and focus group discussions (FGDs) was conducted in October 2018 in Blantyre, Lilongwe, and rural districts of Mzimba North and Mangochi. With support of members of the population, study participants were purposively recruited from 4 MSM-friendly drop-in centers where MSM receive a range of health services to ensure representativeness across sites and age. Participants were asked what they had heard about PrEP, their willingness to use PrEP, their barriers to PrEP use, and their preferences for service delivery. The data were analyzed using a thematic content analysis framework that was predetermined in line with objectives. RESULTS: A total of 109 MSM were interviewed-13 through IDIs and 96 through FGDs. Most participants were aware of PrEP as a new HIV intervention but had limited knowledge related to its use. However, the majority were willing to use it and were looking forward to having access to it. IDI participants indicated that they will be more willing to take PrEP if the dosing frequency were appropriate and MSM were involved in information giving and distribution of the drug. FGD participants emphasized that places of distribution and characteristics of the service provider are the key factors that will affect use. Knowing the benefits of PrEP emerged as a key theme in both the IDIs and FGDs. Participants highlighted barriers that would hinder them from taking PrEP such as side effects which were cited in IDIs and FGDs. Key factors from FGDs include cost, fear of being outed, drug stockouts, fear of being known as MSMs by wives, and lack of relevant information. FGDs cited stigma from health care workers, forgetfulness, and community associated factors. CONCLUSIONS: Despite having inadequate knowledge about PrEP, study participants were largely willing to use PrEP if available. Programs should include an effective information, education, and communication component around their preferences and provide PrEP in MSM-friendly sites.

Perspectives about policy implementation: A learning opportunity from the 2003-2013 Malawi HIV/AIDS Policy.

Introduction: Malawi published its first ever HIV and AIDS policy in 2003. The implementation of the policy provided a very necessary and historic step in Malawi's organized response towards HIV and AIDS. Many achievements were registered in the period this policy was implemented. However, some components of the policy were not well-implemented. Our study explored barriers to implementation of provider initiated HIV testing and counseling (PITC) for sexually transmitted infections (STI) within general outpatient settings. Malawi also launched a revised HIV and AIDS Policy in December 2013. Although not part of this policy analysis, future years of implementation may face related issues observed during the implementation of the 2003-2013 policy. Methods: This is a non-experimental, descriptive study using a case study design. We examined the implementation of provider initiated HIV testing and counseling component of the Malawi HIV and AIDS policy from 2003-2013 focusing on STI and outpatient clinic settings. We sought to understand perspectives of various stakeholders and users of the policy. We conducted in-depth interviews with policy makers, health care worker supervisors, health care workers and health rights activists. Results: Major problems which affected the implementation of the 2003-2013 HIV policy were: selective prioritization of policies by government, lack of involvement of implementers in the policy making process, non-awareness of health workers about the existence of the policy, lack of healthcare worker training, unsatisfactory supervision of policy implementation, poor harmonization of policies, lack of clarity about guidance to those directly implementing, unclear roles and reporting authority among the main national coordinating units. Conclusion: Good leadership, effective coordination, involvement of key players in the policy making process, dissemination to primary users and decentralization or empowerment of local supervisors is key to successful policy implementation.

Safety, Feasibility, and Acceptability of the PrePex Device for Adult Male Circumcision in Malawi.

INTRODUCTION: Nonsurgical adult male circumcision devices present an alternative to surgery where health resources are limited. This study aimed to assess the safety, feasibility, and acceptability of the PrePex device for adult male circumcision in Malawi. METHODS: A prospective single-arm cohort study was conducted at 3 sites (1 urban static, 1 rural static, 1 rural tent) in Malawi. Adverse event (AE) outcomes were stratified to include/exclude pain, and confidence intervals (CIs) were corrected for clinic-level clustering. RESULTS: Among 935 men screened, 131 (14.0%) were not eligible, 13 (1.4%) withdrew before placement, and 791 (84.6%) received the device. Moderate and severe AEs totaled 7.1% including pain [95% CI: 3.4-14.7] and 4.0% excluding pain (95% CI: 2.6 to 6.4). Severe AEs included pain (n = 3), insufficient skin removal (n = 4), and early removal (n = 4). Among early removals, 1 had immediate surgical circumcision, 1 had surgery after 48 hours of observation, 1 declined surgery, and 1 did not return to our site although presented at a nearby clinic. More than half of men (51.9%) reported odor; however, few (2.2%) stated they would not recommend the device to others because of odor. Median levels of reported pain (scale, 1-10) were 2 (interquartile range, 2-4) during application and removal, and 0 (interquartile range, 0-2) at all other time points. CONCLUSIONS: Severe AEs were rare and similar to other programs. Immediate provision of surgical services after displacement or early removal proved a challenge. Cases of insufficient skin removal were linked to poor technique, suggesting provider training requires reinforcement and supervision.

Classification and rates of adverse events in a Malawi male circumcision program: impact of quality improvement training.

BACKGROUND: Assessing safety outcomes is critical to inform optimal scale-up of voluntary medical male circumcision (VMMC) programs. Clinical trials demonstrated adverse event (AE) rates from 1.5 to 8 %, but we have limited data on AEs from VMMC programs. METHODS: A group problem-solving, quality improvement (QI) project involving retrospective chart audits, case-conference AE classification, and provider training was conducted at a VMMC clinic in Malawi. For each identified potential AE, the timing, assessment, treatment, and resolution was recorded, then a clinical team classified each event for type and severity. During group discussions, VMMC providers were queried regarding lessons learned and challenges in providing care. After baseline evaluation, clinicians and managers initiated a QI plan to improve AE assessment and management. A repeat audit 6 months later used similar methods to assess the proportions and severity of AEs after the QI intervention. RESULTS: Baseline audits of 3000 charts identified 418 possible AEs (13.9 %), including 152 (5.1 %) excluded after determination of provider misclassification. Of the 266 remaining AEs, the team concluded that 257 were procedure-related (8.6 AEs per 100 VMMC procedures), including 6 (0.2 %) classified as mild, 218 (7.3 %) moderate, and 33 (1.1 %) severe. Structural factors found to contribute to AE rates and misclassification included: provider management of post-operative inflammation was consistent with national guidelines for urethral discharge; available antibiotics were from the STI formulary; providers felt well-trained in surgical skills but insecure in post-operative assessment and care. After implementation of the QI plan, a repeat process evaluating 2540 cases identified 115 procedure-related AEs (4.5 AEs per 100 VMMC procedures), including 67 (2.6 %) classified as mild, 28 (1.1 %) moderate, and 20 (0.8 %) severe. Reports of AEs decreased by 48 % (from 8.6 to 4.5 per 100 VMMC procedures, p < 0.001). Reports of moderate-plus-severe (program-reportable) AEs decreased by 75 % (from 8.4 to 1.9 per 100 VMMC procedures, p < 0.001). CONCLUSIONS: AE rates from our VMMC program implementation site were within the range of clinical trial experiences. A group problem-solving QI intervention improved post-operative assessment, clinical management, and AE reporting. Our QI process significantly improved clinical outcomes and led to more accurate reporting of overall and program-reportable AEs.

Doubt, defiance, and identity: Understanding resistance to male circumcision for HIV prevention in Malawi.

Global policy recommendations to scale up of male circumcision (MC) for HIV prevention tend to frame the procedure as a simple and efficacious public health intervention. However, there has been variable uptake of MC in countries with significant HIV epidemics. Kenya, for example, has embraced MC and has been dubbed a 'leader' by the global health community, while Malawi has been branded a 'laggard' in its slow adoption of a national programme, with a strong political discourse of resistance forming around MC. Regardless of any epidemiological or technical evidence, the uptake of international recommendations will be shaped by how a policy, and the specific artefacts that constitute that policy, intersect with local concerns. MC holds particular significance within many ethnic and religious groups, serving as an important rite of passage, but also designating otherness or enabling the identification of the social and political self. Understanding how the artefact of MC intersects with local social, economic, and political contexts, is therefore essential to understand the acceptance or resistance of global policy recommendations. In this paper we present an in-depth analysis of Malawi's political resistance to MC, finding that ethnic and religious divisions dominating recent political movements aligned well with differing circumcision practices. Political resistance was further found to manifest through two key narratives: a 'narrative of defiance' around the need to resist donor manipulation, and a 'narrative of doubt' which seized on a piece of epidemiological evidence to refute global claims of efficacy. Further, we found that discussions over MC served as an additional arena through which ethnic identities and claims to power could themselves be negotiated, and therefore used to support claims of political legitimacy.

HPTN 035 phase II/IIb randomised safety and effectiveness study of the vaginal microbicides BufferGel and 0.5% PRO 2000 for the prevention of sexually transmitted infections in women.

OBJECTIVES: To estimate the effectiveness of candidate microbicides BufferGel and 0.5% PRO 2000 Gel (P) (PRO 2000) for prevention of non-ulcerative sexually transmitted infections (STIs). METHODS: Between 2005 and 2007, 3099 women were enrolled in HIV Prevention Trials Network (HPTN) protocol 035, a phase II/IIb evaluation of the safety and effectiveness of BufferGel and PRO 2000 for prevention of STIs, including Neisseria gonorrhoeae (NG), Chlamydia trachomatis (CT) and Trichomonas vaginalis (TV). Incidences of STIs were determined by study arm, and HRs of BufferGel and PRO 2000 versus placebo gel or no gel control groups were computed using discrete time Andersen-Gill proportional hazards model. RESULTS: The overall incidence rates were 1.6/100 person-years at risk (PYAR) for NG, 3.9/100 PYAR for CT and 15.3/100 PYAR for TV. For BufferGel versus placebo gel, HRs were 0.99 (95% CI 0.49 to 2.00), 1.00 (95% CI 0.64 to 1.57) and 0.95 (95% CI 0.71 to 1.25) for prevention of NG, CT and TV, respectively. For PRO 2000, HRs were 1.66 (95% CI 0.90 to 3.06), 1.16 (95% CI 0.76 to 1.79) and 1.18 (95% CI 0.90 to 1.53) for prevention of NG, CT and TV, respectively. CONCLUSIONS: The incidence of STIs was high during HIV Prevention Trials Network 035 despite provision of free condoms and comprehensive risk-reduction counselling, highlighting the need for effective STI prevention programmes in this population. Unfortunately, candidate microbicides BufferGel and PRO2000 had no protective effect against gonorrhoea, chlamydia or trichomoniasis. TRIAL REGISTRATION NUMBER: NCT00074425.

Sexual partnership patterns in malawi: implications for HIV/STI transmission.

BACKGROUND: Concurrent sexual partnerships are believed to play an important role in HIV transmission in sub-Saharan Africa, but the contributions of concurrency to HIV and sexually transmitted infection (STI) spread depend on the details of infectious periods and relationship patterns. To contribute to the understanding of sexual partnership patterns in this region, we estimated partnership lengths, temporal gaps between partners, and periods of overlap across partners at an STI clinic in Lilongwe, Malawi. METHODS: Participants underwent physical examinations and HIV tests, and responded to questionnaires about demographics and risk behaviors, including detailed questions about a maximum of 3 sexual partners in the previous 2 months. We calculated partnership length as the time between the first and most recent sexual contact with a partner, and gap length as the time between the most recent contact with 1 partner and the first contact with the next. We defined concurrent and consecutive partnerships as gap length ≤0 days and gap length >0 days, respectively. RESULTS: In the study population (n = 183), 86% reported 0 or 1 partner, 5% reported multiple consecutive partnerships, and 9% reported concurrency. The mean partnership length was 858 days (median = 176 days). Gaps between consecutive partnerships were short (mean = 21 days), and overlaps across concurrent partners tended to be long (mean = 246 days). CONCLUSIONS: Multiple sexual partnerships were uncommon, and partnerships were long on average. Among those reporting multiple recent partners, both long-term concurrency and narrowly spaced consecutive partnerships could present substantial risk for efficient transmission of HIV and classical STIs.

Impact of aciclovir on ulcer healing, lesional, genital and plasma HIV-1 RNA among patients with genital ulcer disease in Malawi.

OBJECTIVE: By a randomised, double-blind, placebo-controlled trial of aciclovir 800 mg twice daily for 5 days added to the syndromic management of genital ulcer disease (GUD) to determine the impact on ulcer healing and HIV outcomes. METHODS: Patients presenting with GUD in Malawi were evaluated for HIV and herpes simplex virus type-2 (HSV-2) serologies, ulcer aetiology, lesional, genital and plasma HIV-1 RNA and CD4+ count. Patients were followed up at days 2, 4, 7, 14 and 28. The primary study outcome was ulcer healing at day 14, with secondary outcomes being lesional and genital HIV-1 shedding at day 14 and HIV-1 plasma viral load at day 28 among HIV-1/HSV-2 co-infected individuals. RESULTS: Four hundred and twenty-two patients (74% male) were randomised (208 to aciclovir, 214 to placebo), of whom 61% were HIV-1 seropositive and 72% HSV-2 seropositive; 67% (267/398) had HSV-2 ulcers. 85% of ulcers were healed at day 14 with no difference between treatment arms (risk ratio (RR)=1.02, 95% CI 0.93 to 1.11). Among 244 HIV-1/HSV-2 co-infected individuals, aciclovir reduced lesional HIV-1 RNA (adjusted RR=0.64, 95% CI 0.41 to 0.99) and seminal HIV-1 RNA (adjusted RR=0.59, 95% CI 0.40 to 0.88), but not cervical HIV-1 RNA or plasma HIV-1 RNA. CONCLUSIONS: Episodic HSV treatment with aciclovir added to syndromic management did not produce a significant clinical benefit in this African population.

Evaluating nurses' implementation of an infant-feeding counseling protocol for HIV-infected mothers: The Ban Study in Lilongwe, Malawi.

A process evaluation of nurses' implementation of an infant-feeding counseling protocol was conducted for the Breastfeeding, Antiretroviral and Nutrition (BAN) Study, a prevention of mother-to-child transmission of HIV clinical trial in Lilongwe, Malawi. Six trained nurses counseled HIV-infected mothers to exclusively breastfeed for 24 weeks postpartum and to stop breastfeeding within an additional four weeks. Implementation data were collected via direct observations of 123 infant feeding counseling sessions (30 antenatal and 93 postnatal) and interviews with each nurse. Analysis included calculating a percent adherence to checklists and conducting a content analysis for the observation and interview data. Nurses were implementing the protocol at an average adherence level of 90% or above. Although not detailed in the protocol, nurses appropriately counseled mothers on their actual or intended formula milk usage after weaning. Results indicate that nurses implemented the protocol as designed. Results will help to interpret the BAN Study's outcomes.

Morbidity and mortality among a cohort of human immunodeficiency virus type 1-infected and uninfected pregnant women and their infants from Malawi, Zambia, and Tanzania.

BACKGROUND: Morbidity and mortality patterns among pregnant women and their infants (before antiretroviral therapy was widely available) determines HIV-1 diagnostic, monitoring, and care interventions. METHODS: Data from mothers and their infants enrolled in a trial of antibiotics to reduce mother-to-child-transmission of HIV-1 at 4 sub-Saharan African sites were analyzed. Women were enrolled during pregnancy and follow-up continued until the infants reached 12 months of age. We describe maternal and infant morbidity and mortality in a cohort of HIV-1-infected and HIV-1-uninfected mothers. Maternal and infant factors associated with mortality risk in the infants were assessed using Cox proportional hazard modeling. RESULTS: Among 2292 HIV-1-infected mothers, 166 (7.2%) had a serious adverse event (SAE) and 42 (1.8%) died, whereas no deaths occurred among the 331 HIV-1 uninfected mothers. Four hundred twenty-four (17.8%) of 2383 infants had an SAE and 349 (16.4%) died before the end of follow-up. Infants with early HIV-1 infection (birth to 4-6 weeks) had the highest mortality. Among infants born to HIV-1-infected women, maternal morbidity and mortality (P = 0.0001), baseline CD4 count (P = 0.0002), and baseline plasma HIV-1 RNA concentration (P < 0.0001) were significant predictors of infant mortality in multivariate analyses. CONCLUSIONS: The high mortality among infants with early HIV-1 infection supports access to HIV-1 diagnostics and appropriate early treatment for all infants of HIV-1-infected mothers. The significant association between stage of maternal HIV-1 infection and infant mortality supports routine CD4 counts at the time of prenatal HIV-1 testing.

The year-long effect of HIV-positive test results on pregnancy intentions, contraceptive use, and pregnancy incidence among Malawian women.

OBJECTIVES: To estimate the effect of receiving HIV-positive test results on intentions to have future children and on contraceptive use and to assess the association between pregnancy intentions and pregnancy incidence among HIV-positive women in Malawi. METHODS: Women of unknown HIV status completed a questionnaire about pregnancy intentions and contraceptive use and then received HIV voluntary counseling and testing (VCT). Women who were HIV-positive and not pregnant were enrolled and followed for 1 year while receiving HIV care and access to family planning (FP) services. RESULTS: Before receiving their HIV test results, 33% of women reported a desire to have future children; this declined to 15% 1 week later (P < 0.0001) and remained constant throughout follow-up. Contraceptive use increased from 38% before HIV testing to 52% 1 week later (P < 0.0001) and then decreased to 46% by 12 months. The pregnancy incidence among women not reporting a desire to have future children after VCT was less than half of the incidence among women reporting this desire. CONCLUSIONS: With knowledge of their HIV-positive status, women were less likely to desire future pregnancies. Pregnancy incidence was lower among women not desiring future children. Integration of VCT, FP, and HIV care could prevent mother-to-child HIV transmission.

Improved detection of acute HIV-1 infection in sub-Saharan Africa: development of a risk score algorithm.

OBJECTIVE: Individuals with acute (preseroconversion) HIV infection (AHI) are important in the spread of HIV. The identification of AHI requires the detection of viral proteins or nucleic acids with techniques that are often unaffordable for routine use. To facilitate the efficient use of these tests, we sought to develop a risk score algorithm for identifying likely AHI cases and targeting the tests towards those individuals. DESIGN: A cross-sectional study of 1448 adults attending a sexually transmitted infections (STI) clinic in Malawi. METHODS: Using logistic regression, we identified risk behaviors, symptoms, HIV rapid test results, and STI syndromes that were predictive of AHI. We assigned a model-based score to each predictor and calculated a risk score for each participant. RESULTS: Twenty-one participants (1.45%) had AHI, 588 had established HIV infection, and 839 were HIV-negative. AHI was strongly associated with discordant rapid HIV tests and genital ulcer disease (GUD). The algorithm also included diarrhea, more than one sexual partner in 2 months, body ache, and fever. Corresponding predictor scores were 1 for fever, body ache, and more than one partner; 2 for diarrhea and GUD; and 4 for discordant rapid tests. A risk score of 2 or greater was 95.2% sensitive and 60.5% specific in detecting AHI. CONCLUSION: Using this algorithm, we could identify 95% of AHI cases by performing nucleic acid or protein tests in only 40% of patients. Risk score algorithms could enable rapid, reliable AHI detection in resource-limited settings.

Amplified transmission of HIV-1: comparison of HIV-1 concentrations in semen and blood during acute and chronic infection.

OBJECTIVES: This study was conducted to compare viral dynamics in blood and semen between subjects with antibody negative, acute HIV-1 infection and other subjects with later stages of infection. DESIGN: A prospective cohort study was embedded within a cross-sectional study of HIV screening in a Lilongwe, Malawi STD clinic. METHODS: Blood samples from HIV antibody negative or indeterminate volunteers were used to detect HIV RNA in plasma using a pooling strategy. Blood and seminal plasma HIV-1 RNA concentrations were measured over 16 weeks. RESULTS: Sixteen men with acute HIV infection and 25 men with chronic HIV infection were studied. Blood viral load in subjects with acute HIV infection was highest about 17 days after infection (mean +/- SE, 6.9 +/- 0.5 log10 copies/ml), while semen viral load peaked about 30 days after infection (4.5 +/- 0.4 log10 copies/ml). Semen viral load declined by 1.7 log10 to a nadir by week 10 of HIV infection. Semen and blood viral loads were more stable in chronically infected subjects over 16 weeks. Higher semen levels of HIV RNA were noted in subjects with low CD4 cell counts. CONCLUSIONS: These results provide a biological explanation for reported increases in HIV transmission during the very early (acute) and late stages of infection. Recognizing temporal differences in HIV shedding in the genital tract is important in the development of effective HIV prevention strategies.

Rapid, real-time detection of acute HIV infection in patients in Africa.

BACKGROUND: We conducted a prospective study to evaluate methods of detecting clients with sexually transmitted diseases (STDs) who were acutely coinfected with human immunodeficiency virus (HIV) in Lilongwe, Malawi. METHODS: After informed consent was obtained, all clients with acute STDs were offered voluntary HIV counseling and testing by 2 rapid antibody tests. Samples from rapid test-negative or -discordant subjects were pooled (50 : 5 : 1) and tested for HIV RNA. Western blots were performed on all rapid test-discordant specimens with detectable HIV RNA. A subset of specimens received p24 antigen testing with standard and/or ultrasensitive methods. Patients with possible acute HIV infection were followed to confirm seroconversion. RESULTS: A total of 1450 clients (34% female and 66% male) agreed to testing, of whom 588 (40.55%) had established HIV infection and 21 (1.45%) had acute infection. Discordant rapid antibody tests identified 7 of 21 (33.3% sensitivity), standard p24 antigen identified 12 of 16 (75% sensitivity), and ultrasensitive p24 antigen identified 15 of 17 (88% sensitivity) acute cases. By definition, the sensitivity of the RNA assay was 100%. CONCLUSIONS: Real-time pooled RNA testing for the detection of acute HIV infection is feasible in resource-limited settings. However, parallel rapid testing and p24 antigen testing are technologically simpler and together may detect approximately 90% of acute cases.

The cost-effectiveness of treating male trichomoniasis to avert HIV transmission in men seeking sexually transmitted disease care in Malawi.

OBJECTIVE: Allocation of funds to program areas where they may have an impact is critical to the success of any HIV control program. We examined the cost-effectiveness of providing first-line treatment for male trichomoniasis in Malawi, a condition not commonly considered in syndromic management throughout sub-Saharan Africa. METHODS: We used decision tree analysis to assess program costs and outcomes among a 1-year population of male sexually transmitted disease (STD) clinic attendees estimated at 10,000 in Lilongwe. Our main outcomes were program costs from the government perspective and HIV infections averted. We conducted univariate and multivariate sensitivity analyses on selected parameters. RESULTS: In our study population of male STD clinic attendees with an HIV prevalence of 44% and a Trichomonas vaginalis prevalence of 20%, including universal metronidazole as a first-line treatment for trichomoniasis at $0.05 per dose would increase program costs by $277 (year 2000 US dollars) and avert 23 cases of HIV. The incremental cost-effectiveness ratio (ICER) over the current STD management guidelines was $15.42 per case of HIV averted. The number of HIV infections averted under sensitivity analysis ranged from 2 to 52, with attendant ICERs varying from cost savings to $162.92. Consideration of wider social benefits, such as the costs of HIV infections to the individual or the government, would further enhance the cost-effectiveness of this program. CONCLUSIONS: As part of a larger program to control STDs, incorporating metronidazole to treat male trichomoniasis could represent a cost-effective means to reduce HIV transmission in this high-risk group.

HIV incidence among women of reproductive age in Malawi and Zimbabwe.

OBJECTIVE: The objective of this study was to determine the incidence of HIV-1. GOAL: The goal of this study was to inform HIV prevention and vaccine trials by conducting a multisite study in Malawi and Zimbabwe. STUDY DESIGN: Women of reproductive age were enrolled in a prospective study. They received 5 intensive HIV counseling and condom promotion sessions over 2 months. Subsequently, HIV-negative women completed quarterly follow-up visits. HIV incidence rates and predictors of HIV acquisition were assessed. RESULTS: A total of 2016 HIV-negative women were enrolled in the condom promotion and counseling phase of the study. Of these, 1679 were tested for HIV during follow up and 113 women seroconverted, resulting in an overall HIV incidence rate of 4.7 per 100 women-years (95% confidence interval = 3.8-5.6). Incidence rates were similar across sites. The major predictors of HIV acquisition were young age, presence of sexually transmitted infections, being unmarried, and higher educational level. CONCLUSION: The incidence of HIV continues to be high among women in both Malawi and Zimbabwe despite counseling and condom promotion.

Nonoxynol-9 100 mg gel: multi-site safety study from sub-Saharan Africa.

OBJECTIVES: To evaluate the safety of 100 mg nonoxynol-9 (N-9) gel, a vaginal microbicide, on the genital mucosa of women from Malawi and Zimbabwe in preparation for a phase III efficacy study. METHODS: HIV-uninfected women (180) were enrolled and randomized to either N-9 or placebo gel and instructed to insert gel into the vagina twice daily for 14 days. Follow up examinations were conducted at 7 and 14 days. RESULTS: The number of adverse events in the N-9 gel group was higher than in the placebo group (40% versus 13%; P < 0.01). Reported number of any genital symptoms was significantly higher in the N-9 group (38% N-9, 13% placebo; P = 0.01). The number of total epithelial disruptions was higher in the N-9 group (20% versus 3%; P < 0.01); however, the number of genital ulcers and abrasions in the N-9 group was low (2% and 3%, respectively) and not different from that in the placebo group (1% and 2%, respectively). CONCLUSIONS: N-9 gel 100 mg caused a significant increase in the rate of genital symptoms and epithelial disruptions compared with placebo. The clinical significance of these epithelial disruptions is unknown. Although these findings alone were not sufficient to cancel the planned phase III study, when considered together with the negative results from the COL-1492 effectiveness trial of 52.5 mg N-9 gel, the decision was made to cancel the planned phase III trial of 100 mg N-9 gel.

HIV-1 populations in blood and breast milk are similar.

Mother-to-child transmission (MTCT) of human immunodeficiency virus type 1 (HIV-1) through breast milk is a significant mechanism of infection in many regions of the world. We compared the HIV-1 populations in paired blood and breast milk samples using a heteroduplex tracking assay (HTA) for the V1/V2 regions of env (V1/V2-HTA). V1/V2-HTA patterns were similar in the eight pairs of samples for which adequate template sampling could be demonstrated. No unique variants existed in either compartment, and differences detected in the relative abundance of variants between compartments were small, occurred among low abundance variants, and were not statistically significant. We also documented the impact of template sampling as a limiting feature in comparing two viral populations. The absence of unique variants and the lack of significant differences in the relative abundance of variants between these compartments support the conclusion that viruses in the blood plasma and breast milk are well equilibrated.